This invention relates to an improved vehicle for topical applied medicinal or cosmetic products. The vehicle is a stable water-in-oil emulsion which is not significantly diluted by perspiration, rain, showering, or swimming. The vehicle of this invention then is suitable for application of a medicinal composition to alleviate skin disorders associated with inflammation, for example, or for incorporating a sun protective agent to prevent the harmful effects of sunlight on the human skin.
Two types of emulsions are commonly known. These emulsions are either the oil-in-water (o/w) or water-in-oil emulsions (w/o). In the former, water is the external phase or the dispersion medium, and in the latter, oil is the external phase with water being the dispersed phase. Oil-in-water emulsions are water washable and are the vehicles used in most cosmetic and pharmaceutical products.
In contrast, water-in-oil emulsions are water non-washable vehicles which are not widely used in either cosmetic or pharmaceutical products. Water-in-oil emulsions possess two distinct properties. These properties are substantiation and occlusion after application onto the skin. Therefore a water-in-oil cream is not significantly diluted by perspiration. In addition, application of a water-in-oil emulsion to skin disorders such as dry skin or inflammatory skin, will result in a protective or occlusive effect on the lesions.
There are two major problems associated with water-in-oil emulsions however. In the past, these emulsions have not exhibited storage stability, and when topically applied, these emulsions exhibit a greasy feeling on the skin. Known past attempts at formulating water-in-oil emulsion vehicles have been unsuccessful in both eliminating a greasy feeling and in providing realistic storage stability.
In water-in-oil emulsions, where water is the internal phase, theoretically, there is a maximum limit on the water content and a minimum requirement for the oil concentration. For example, in non-ionic water-in-oil emulsions, the theoretical maximum water content is 74%. In actuality, water content, normally, is 50% or less. Even at this concentration, the formulation of a true water-in-oil emulsion that is thermally stable, e.g. at 50.degree. C. for an extended period of time, is a great challenge.
In an ionic water-in-oil emulsion, the water content is usually 35% or less. For example, one of the most well known ionic water-in-oil emulsions is the beeswax-borax cream which consists of the following ingredients: sorbitan sesquioleate, 1 part; mineral oil, 50 parts; beeswax, 10 parts; lanolin, 3.1 parts; borax, 0.7 parts; and water, 35.2 parts. This cream, due to the lanolin and high mineral oil content, feels quite greasy to the touch. In addition, this emulsion breaks down after storage after about one month at 50.degree. C. Furthermore, borax is not a risk-free substance. Therefore, there exists a need for a more stable formulation that is safe to use.
In formulating water-in-oil emulsions, one of the most frequently observed difficulties is the appearance of a transparent oil layer at the surface. It has been suggested that the addition of small amounts of polyvalent metal soaps such as magnesium sulfate in a concentration of 0.1 to 0.2% to the emulsion during preparation will help resist this instability. However, under test conditions, neither magnesium sulfate, nor compounds such as magnesium chloride, aluminum oxide, aluminum hydroxide, zinc oxide, zinc hydroxide, ferric sulfate, ferric hydroxide, basic calcium phosphate, or calcium carbonate were effective in stabilizing water-in-oil emulsions under the test conditions to be hereinafter described.
A recent report by P. Thau entitled "Stabilization of Water-in oil Emulsion by in situ Formation of Calcium Soaps" Cosmetics and Toiletries 92 57-59, (1977) indicates that calcium saccharate can enhance the thermal stability of water-in-oil emulsions. Calcium saccharate is a complex mixture of 2 moles of sucrose with 1 mole of calcium oxide. It has been speculated that calcium saccharate enhances the stability of water-in-oil emulsions by allowing the in situ formulation of a high concentration of calcium stearate or calcium oleate. Calcium hydroxide has also been noted to exert a similar effect after being mixed with sucrose or other sugars.
However, it has been discovered that the in situ formation of soaps such as calcium stearate or sodium stearate does not enhance the thermal stability of water-in-oil emulsions. On the contrary, the above soaps appeared to exert an unstabilizing influence on water-in-oil emulsions. Water-in-oil emulsions were formulated for testing between stearic acid and each of the following compounds: calcium hydroxide, monobasic sodium phosphate, dibasic sodium phosphate, sodium silicate, and calcium gluconate. These emulsions were then tested for stability at 50.degree. C. and in each instance, the emulsion destabilized and broke.
It has been discovered however, that water-in-oil emulsions may be successfully stabilized even at high water concentrations by the addition of a small concentration of magnesium oxide or magnesium hydroxide. According to this invention, it has been discovered that stearic acid or other fatty acids are not required in emulsion formulations, and special equipment or mixing procedures are also not necessary in order to prepare stable emulsions. Ordinary, commercially available mixing equipment is sufficient for preparation of the water-in-oil emulsions of this invention.
The therapeutic use of magnesium hydroxide for either internal or topical application is the subject of several prior U.S. Patents. For example, in U.S. Pat. No. 1,384,460 and emulsion, for internal use, of mineral oil and milk of magnesia is described. In addition, in U.S. Pat. Nos. 1,999,160 and 1,999,161, the topical application of magnesium hydroxide in a skin-cleansing cream containing from 0.5 to 6% magnesium hydroxide is described. The skin cleansing cream, however, utilizes beeswax and borax as an emulsifying agent and incorporates magnesium hydroxide as an astringent which is sufficiently alkaline to neutralize acid excretions found on the skin.
In addition, U.S. Pat. No. 2,414,024 describes an oil-in-water emulsion utilizing magnesium hydroxide. This patent, however, describes an emulsion of increased stability due to the presence of an alkaline earth salt of a cyclic or substituted cyclic acid in addition to a magnesium hydroxide suspension therein.
In accordance with the present invention, however, magnesium oxide or magnesium hydroxide is incorporated into an emulsion composition during the preparation thereof. The concentration of magnesium hydroxide or magnesium oxide may vary from 0.02 to 2% by weight of the total composition, and the preferred concentration range is from 0.1 to 0.5% thereof. The magnesium oxide or magnesium hydroxide stabilizing agent may be incorporated in either the oil phase or the aqueous phase before mixing or may be added to the emulsion after mixing.
The oil phase may consist of one or more well known products such as petrolatum, mineral oil, beeswax, isopropyl myristate, isopropyl palmitate, squalene, squalane, tocopheryl acetate, lanolin, wax, spermaceti, hydrogenated vegetable oil, chicken oil, or suet fat. The emulsifier may be a compound such as sorbitan monooleate, sorbitan sesquioleate, or sorbitan trioleate. A combination of ingredients in the oil phase may utilize each of the foregoing ingredients in a range of from 0 to 20% by weight of the total composition, but the preferred concentration range is up to 10% thereof.
The aqueous phase may consist of water, sorbitol, propylene glycol, 1,3-butanediol, and glycerin. The concentration of water may range up to 70% by weight of the total composition with the preferred concentration range being from 30 to 60% thereof. The concentration of sorbitol, propylene glycol, 1,3-butanediol, or glycerin may range up to 10% by weight of the total composition, with the preferred concentration range being from 2 to 5% thereof.
In preparing the water-in-oil emulsions of this invention, the oil phase and the aqueous phase preferably are separately heated to 75.degree.-80.degree. C., and the aqueous phase slowly poured into the oil phase with agitation. Agitation is continued until the mixture congeals. Any preservative or fragrance desired may be added to the water-in-oil emulsion without affecting its stability. After the emulsion is formed, other cosmetic ingredients or pharmaceutical drugs may be incorporated therein. For example, hydrocortisone has been incorporated in a water-in-oil emulsion of the present invention at a concentration of 1% by weight of the total composition.
It has been established in extensive tests that magnesium oxide or magnesium hydroxide in a concentration of from 0.02 to 2% and preferably from 0.1 to 0.5% thereof stabilizes a water-in-oil emulsion. Emulsions of this invention have been successfully stored for two months at 50.degree. C., and have been shown to be stable after freezing and thawing. Both therapeutic and cosmetic agents have been incorporated in emulsions of this invention successfully. As noted above, a hydrocortisone water-in-oil emulsion of this invention was formulated. This composition was tested on humans having eczema and psoriasis and was proven to be therapeutically effective when applied on a daily basis to cause within about one week's time a return of the affected area to normal skin condition. Furthermore, the sun-screen agent p-aminobenzoic acid or its ester has been incorporated in water-in-oil emulsions of this invention in concentrations of from 1 to 10% and have proven effective in preventing harmful damage to the skin caused by sunlight.
It has also been established in extensive tests that the emulsions of this invention when used as a vehicle for therapeutic compositions useful in treating inflammatory skin diseases by topical application produce a therapeutically superior medicinal composition. The emulsions of this invention have been shown to improve the ability of such compounds as hydrocortisone, hydrocortisone 17-valerate, triamcinolone acetonide, 6-aminonicotinamide, and 6-aminonicotinic acid methyl ester to alleviate the symptoms of inflammatory skin diseases such as psoriasis, dermatitis, and eczema.
Inflammatory skin diseases are clinically characterized by redness, swelling and heat, and may or may not be accompanied by an itching sensation or pain. In clinical treatment of most inflammatory skin disorders, including psoriasis, dermatitis and eczema, tests have shown that the most prompt relief and healing is obtained with the medicinal ingredient incorporated in a vehicle containing water which is applied to the skin, and the area effected covered with an occlusive dressing such as a plastic film. A vehicle then most useful in the treatment of inflammatory skin diseases optimally possess two distinct properties, (A) providing moisture, and (B) providing occlusion.
Since an oil-in-water (O/W) emulsion has water in the external phase and oil as a dispersion medium, use of this type of emulsion in treatment of inflammatory skin diseases provides only moisture, but not occlusion. In contrast, petrolatum, provides occlusion, but no moisture.
While it is not known with certainty, it is believed that enhanced curing achieved with the water-in-oil (W/O) emulsion of the present invention lies in the fact that such a vehicle provides both moisture and occlusion. Oil is the external phase with water being the dispersed phase. Therefore, the water-in-oil emulsion of the present invention provides both moisture and occlusion and the tests, as will be subsequently described, have shown such an emulsion to be more efficacious than the same concentration of active ingredient in an oil-in-water emulsion such as hydrophilic ointment, or in petrolatum.
Accordingly, it is an object of this invention to provide a stabilizing agent for water-in-oil emulsions useful as vehicles for cosmetics or for medicinal applications.
It is another object of this invention to incorporate magnesium oxide or magnesium hydroxide in conventional water-in-oil vehicles to stabilize said vehicles.
It is another object of this invention to provide a medicinal composition containing a pharmaceutical compound in a stable water-in-oil emulsion which, when topically applied, will alleviate symptoms of inflammatory diseases.
It is still another object of this invention to provide a cosmetic composition containing a sun-protective agent in a stable water-in-oil emulsion which, when topically applied, will reliably prevent damage to the skin by sunlight.
It is still another object of this invention to provide a method for stabilizing water-in-oil emulsions with magnesium oxide or magnesium hydroxide.
These and other objections will become readily apparent with reference to the following description.
The following are illustrative examples of formulations of water-in-oil emulsions useful as vehicles for topical application according to this invention. It should be understood that the following examples are illustrative only and not limitative of the invention. Therefore, any of the aforementioned wax, fat or oil compositions may be substituted according to the teachings of this invention in the following formulations.